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Biomedical subjects

T Ikeda

Publications and source records attributed to T Ikeda.

At least 307 records · Page 17Linked to original sources
PubMed2000

Characterization of UDP-glucuronosyltransferases (UGTS) involved in the metabolism of troglitazone in rats and humans.

UDP-glucuronosyltransferases (UGTs) involved in troglitazone glucuronidation in rats and humans have been characterized to support the previous toxicity study on troglitazone in Gunn rats and to examine whether the UGT polymorphism or inhibition of bilirubin metabolism is related to the clinically reported rare cases of liver failure. The experiments using Gunn rats revealed that UGT1 enzymes are not involved in troglitazone glucuronidation and that the responsible enzyme in rats was suggested to be UGT2B2, an androsterone UGT, by inhibition studies. In humans, contribution of UGT1A1 was estimated to be about 30% of the total troglitazone glucuronidation by UGTs, using human liver microsomes and recombinant UGTs. Other UGT1 and UGT2 enzymes seem to be responsible for the rest of the troglitazone glucuronidation in humans. The multiplicity of UGTs involved in troglitazone glucuronidation in humans may allow even patients lacking bilirubin UGT (UGT1A1) activity to produce troglitazone glucuronide. These observations suggest that the polymorphism of UGT is not the reason behind the liver failure induced by the troglitazone treatment, and troglitazone does not inhibit bilirubin glucuronidation in clinical treatment. In addition, the increased bilirubin level in the blood of patients who have troglitazone-induced liver failure is a consequence of liver injury and not due to inhibition of bilirubin glucuronidation by troglitazone.

Animals↗
PubMed2000

Comparison of sperm motility test methods (except computer-assisted sperm analysis) in rats under the condition of alfa-chlorohydrin treatment--collaborative investigation.

A comparison among rat sperm motility test methods including percent of motile sperm (% Motile), scoring method (Scoring), Ishii's method, Progressive Motility Test (PMT) and Sperm Quality Analyzer (SQA), was conducted using data gathered from eleven laboratories. As a unified study design, mature male rats were orally treated daily for approximately 1 week with alpha-chlorohydrin (ACH), which is known to affect the sperm motility at the epididymis, at dose levels of 2.5, 5 and 10 mg/kg, and then subjected to more than two test methods for sperm motility in each laboratory. Scoring (4 or 5 grades), Ishii's method, PMT and SQA showed high sensitivity for the detection of the effects of ACH, which were not considered to be inferior to a computer-assisted sperm analyzer (CASA). Longer incubation time before testing was considered to contribute to detecting the effects of ACH. In particular, we realized that Scoring was a favorable method even if the demerit of poor objectivity was allowed for. Percent Motile showed lower sensitivity than other test methods. The differences in sensitivity between % Motile and other methods were considered to be based on whether the defects of progressive motion could be detected. Although % Motile cannot clearly judge whether immotile sperm are dead or alive, the value is a great help for the interpretation of the result from other methods. Based on the characters for detectability, objectivity and efficiency, the most suitable method of sperm motility should be selected according to the purpose of the toxicity study.

Animals↗
PubMed2000

Air leak syndrome as one of the manifestations of bronchiolitis obliterans organizing pneumonia.

A 46-year-old man developed respiratory distress with air leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema. Open lung biopsy was performed and revealed the histopathologic evidence of bronchiolitis obliterans organizing pneumonia (BOOP), which responded well to steroid treatment. As far as we know, this appears to be the first case of BOOP presenting with ALS as one of its major complications.

Biopsy↗
PubMed2000

Undefined complications of parathyroid adenoma, parathyroid hyperplasia (primary hyperparathyroidism), thyroid follicular adenoma, thyroid papillary carcinoma, temporal astrocytoma, cerebellar meningioma, and hemangioma of external auditory meatus and oral papilloma.

A 59-year-old woman who had parathyroid adenoma, parathyroid hyperplasia, thyroid follicular adenoma, thyroid papillary carcinoma, astrocytoma of the right temporal lobe, cerebellar meningioma, capillary hemangioma of the left external auditory meatus and papilloma of the left upper gingiva is reported. Dynamic magnetic resonance imaging, computed tomography with contrast-enhancement and gastrofiberscopy revealed no remarkable findings in the pituitary, pancreas, adrenals, stomach or duodenum. Similar lesions were not found in any family members. Defect of the causative genes of multiple endocrine neoplasia types I and IIa, MENIN and RET was not detected. Further follow-up of this patient and family members is needed.

Adenoma↗
PubMed2000

Expression levels of thymidine phosphorylase and dihydropyrimidine dehydrogenase in various human tumor tissues.

Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine), an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil (5-FUra), while dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra to an inactive molecule. The susceptibility of tumors to fluoropyrimidines is reported to correlate with tumor levels of these enzymes. To obtain some insight into the tumor types susceptible to fluoropyrimidine therapy, we measured expression levels of these two enzymes in various types of human cancer tissues (241 tissue samples) by the ELISA methods. DPD exists in all the cancer types studied, such as bladder, breast, cervical, colorectal, esophageal, gastric, hepatic, pancreatic, prostate, and renal cancers. Among them, the cervical, hepatic, pancreatic, esophageal, and breast cancer tissues expressed high levels of DPD (median >70 U/mg protein), while high concentrations of the dThdPase were expressed in esophageal, cervical, breast, and pancreatic cancers and hepatoma (median >150 U/mg protein). The dThdPase/DPD ratio, which was reported to correlate with the susceptibility of human cancer xenografts to capecitabine, was high in esophageal, renal, breast, colorectal, and gastric cancers (median ratio of >1.5). In any of these three parameters, the inter-patient DPD variability for each cancer type was much larger than the DPD variability among cancer types; highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD were 10-321, 7-513, and 2-293, respectively. These results indicate that measurements of the three parameters, DPD, dThdPase and dThdPase/DPD, would be useful criteria for selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

Animals↗
PubMed2000

[Second reconstructions after failure of free-tissue transfer in the head and neck region].

A retrospective study was performed on 74 patients seen in our hospital between 1990 and 1999 who underwent head and neck reconstructive surgery involving a free flap. Reconstructive surgery was unsuccessful in 5 cases (6.8%). A pedicled myocutaneus flap was used in two cases for the second reconstruction attempt, while a second free flap (jejunum) was used in two other patients. In these cases, a bilateral neck dissection was performed prior to the second free flap reconstruction and neck infection was found. The head and neck artery and vein were unsuitable as recipient vessels in the second operation. Instead, the cephalic vein was used as a source of vein grafts and as a recipient vein.

Adult↗
PubMed2000

Changes in vitreous concentrations of human hepatocyte growth factor (hHGF) in proliferative diabetic retinopathy: implications for intraocular hHGF production.

We measured human hepatocyte growth factor (hHGF) concentrations in the original vitreous and in the artificial vitreous after vitrectomy in 13 patients with proliferative diabetic retinopathy (PDR) undergoing repeated pars plana vitrectomy, in order to investigate whether the vitreous hHGF concentration is related to the recurrence of PDR after vitrectomy as well as to the original occurrence of PDR. We also examined the relationship between vitreous concentrations of hHGF and transforming growth factor-beta(2) (TGF-beta(2)), the predominant TGF-beta isoform in the vitreous, in 14 patients with PDR. For the original vitreous, mean hHGF concentrations were higher (P<0.05) in that from patients with severe PDR (vitreous haemorrhage, fibrovascular proliferation and tractional retinal detachment) than in that from patients with vitreous haemorrhage alone. In the artificial vitreous, mean vitreous hHGF concentrations were higher (P<0.05) in that from patients with severe PDR than in that from patients with vitreous haemorrhage alone or with vitreous haemorrhage plus fibrovascular proliferation. No correlation was found between the hHGF concentration in the artificial vitreous and time between vitrectomies. Vitreous hHGF concentrations were directly proportional to vitreous concentrations of latent TGF-beta(2) (r=0. 831; P=0.0002), but inversely proportional to vitreous concentrations of active TGF-beta(2) (r=0.495; P=0.072), which inhibits hHGF production. A decreased conversion of latent into active TGF-beta(2) in ocular disorders such as PDR is likely to result in an increased concentration of hHGF in the vitreous. Thus intraocular hHGF may be involved in pathological mechanisms causing not only the occurrence, but also the recurrence, of PDR.

Adult↗
PubMed2000

Soluble Fas ligand expression in the ocular fluids of uveitis patients.

PURPOSE: The expression of Fas ligand (FasL) in ocular tissues is thought to play a critical role in maintaining immune privilege in the eye. In this study, to clarify the involvement of the Fas-FasL system in inflammatory processes of the eye,we examined soluble FasL (sFasL) in ocular inflammation. METHODS: Using ELISA systems recently developed, sFasL concentrations in aqueous humor (AH) and/or vitreous fluid (VF) were measured. AH was obtained from 17 eyes of 17 uveitis patients and from 12 eyes of 12 non-uveitis (cataract) patients. VF was obtained from 22 eyes of 22 uveitis patients and 7 eyes of 7 non-uveitis (macular hole) patients. Serum levels of sFasL were also determined. RESULTS: sFasL in AH and VF was below the detection limit of the ELISA systems in all non-uveitis eyes. On the other hand, sFasL was detected in AH from uveitis patients where it measured 367.0 +/- 154.7 pg/ml (mean +/- SEM). sFasL was also detected in VF from uveitis patients where it measured 1132.2 +/- 281.7 pg/ml. None of the sera from patients with or without uveitis contained a detectable level of sFas L. CONCLUSIONS: sFasL levels in AH and VF are elevated in the eye during ocular inflammation. Fas-FasL mediated apoptosis may play an important role in the regulation of inflammation during uveitis.

Aged↗
PubMed2000

Improving effects of topical administration of iganidipine, a new calcium channel blocker, on the impaired visual evoked potential after endothelin-1 injection into the vitreous body of rabbits.

PURPOSE: To investigate the effect of topical iganidipine, a new dihydropyridine derivative calcium channel blocker, on impairment of the ocular circulation caused by endothelin-1 (ET-1), we examined modification of the effect of ET-1 on visual-evoked potential (VEP) in albino rabbits. METHODS: To clarify whether VEP could be used to indicate the extent of ocular circulatory impairment, we evaluated the dose dependency of changes in VEP over 2 hours after intravitreal injection of 3 ET-1 doses (1.0, 3.3, or 10 pmol) and the vehicle. Then modification of the effect of ET-1 on the VEP by iganidipine was examined. One hour after the topical instillation of 0.1% iganidipine (20 microl) or its vehicle, 10 pmol of ET-1 was injected into the vitreous in rabbits. The VEP was measured for 2 hours after ET-1 application, and the response was compared between the eyes with iganidipine and vehicle pretreatment. RESULTS: Intravitreal injection of ET-1 dose-dependently reduced the VEP amplitude. Topical administration of 0.1% iganidipine significantly suppressed the reduction of VEP amplitude for the entire 2-hour monitoring period after intravitreal injection of 10 pmol ET-1. There was no significant change of the systemic blood pressure as well as intraocular pressure after topical administration of iganidipine. CONCLUSIONS: Iganidipine eyedrops may be useful for the treatment of ischemic retinal and optic nerve disorders related to abnormal ET-1 production for the maintenance of visual function.

Administration, Topical↗
PubMed2000

[Cardiac tamponade due to ruptured intramural hematoma of the ascending aorta: a case report].

A 72-year-old man with a history of hypertension for 20 years was admitted with symptoms of acute aortic dissection. Computed tomography showed a crescentic thickening of the ascending aortic wall, suggesting an intramural hematoma. Sixteen hours after admission, he underwent urgent repair of the ascending aorta because of cardiac tamponade. We inspected the inside of the aorta from the aortic valve to the arch. Subadventitial hematoma due to hemorrhage from the outer media was confirmed. Rupture of the vasa vasorum was thought to be an initiating mechanism. The affected aortic wall was simply resutured and was not replaced with a graft because the intima was intact and the media was not dissected and the aortic wall was considered to be tolerable to normal blood pressure. The patient continues to do well 18 months following operation. An intramural hematoma of the ascending aorta should be regarded as a precursor of imminent rupture or classic dissection.

Aged↗
PubMed2000

Effect of nitric oxide synthase inhibitor on optic nerve head circulation in conscious rabbits.

PURPOSE: To study the effect of a nitric oxide synthase inhibitor on tissue circulation in the optic nerve head (ONH) of conscious rabbits. METHODS: N(G)-nitro-L-arginine methyl ester (L-NAME) (1, 10, or 100 mg/kg), D-NAME (10 mg/kg), or physiological saline was administered intravenously to albino rabbits. A quantitative index of blood velocity, the normalized blur (NB), was measured in the ONH by laser speckle tissue circulation analyzer. The intraocular pressure (IOP) and blood pressure (BP) were also measured. L-arginine (10 mg/kg) was intravenously administered 20 minutes after L-NAME (10 mg/kg) injection. Acetylcholine (ACh; 10 microg/kg per minute) was infused for 15 minutes, with or without pretreatment of L-NAME (1 mg/kg). RESULTS: L-NAME induced a continuous decrease of the NB in a dose-dependent manner, but D-NAME caused no significant change. At 100 mg/kg, L-NAME significantly increased the IOP, mean BP, and ocular perfusion pressure, but the other doses caused no significant changes. When L-arginine was administered after L-NAME injection, the NB returned to its initial level and remained there. Pretreatment with L-NAME inhibited the increase of NB induced by ACh. CONCLUSIONS: These results indicate that nitric oxide regulates basal tissue circulation in the ONH of conscious rabbits and suggest that ACh increases the circulation by promoting nitric oxide synthesis.

Acetylcholine↗
PubMed2000

Perception of surrounding space controls posture, gaze, and sensation during Coriolis stimulation.

BACKGROUND: Motion sickness evokes not only discomfort but also marked equilibrium ataxia. However, its mechanism of ataxia remains unclear. HYPOTHESIS: We supposed that stance, gaze, and sensation may be uniformly controlled by the perception of the surrounding space. METHODS: Using Coriolis stimulation, we examined eight normal subjects and two patients with bilateral labyrinthine loss. They were asked to stand on a platform; then while being rotated clockwise 60 degrees x s(-1), they tilted their head 30 degrees. Displacement of the center of pressure and ocular movements were recorded using a force platform set on the device and an infrared CCD-video camera fixed to goggles, respectively. RESULTS: In normal subjects with eyes covered, tilting of the head resulted in shifts of the center of pressure and torsional or vertical nystagmus. When they could see the surroundings, they showed stable posture and optokinetic nystagmus regardless of head tilting status. In contrast, the two patients were not affected by head tilting when their eyes were covered, although they showed remarkable body swaying even while they were static. CONCLUSIONS: From the present study, it seems probable that posture, gaze, and sensation are absolutely controlled by the perception of surrounding space, which may be theoretically represented as a vector in the head.

Adult↗
PubMed2000

[The validity of the sentinel node concept in gastrointestinal cancers].

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

Gastrointestinal Neoplasms↗
PubMed2000

[MRI of ductal carcinoma in situ of the breast: patterns of findings and evaluation of disease extent].

Ten cases of ductal carcinoma in situ (DCIS) or DCIS with microinvasion were reviewed in order to evaluate the characteristic findings of DCIS and to evaluate the extent of disease on MRI. A 1.5Tesla Signa or Horizon (GE Medical Systems) unit was used with a dedicated receive-only breast coil. The pulse sequence based on RARE was used with the fat suppression technique. After examining both breasts with a large FOV (30 cm), the affected breast alone was examined with a smaller FOV (18 cm) and larger matrix (512 x 384) with and without Gd-enhancement. DCIS showed several types of findings on MRI: linear, spotty enhancement; gathering of linear enhancement; enhanced area or mass without distortion of the surrounding tissue; and well-circumscribed mass mimicking intraductal papilloma. Compared with typical findings of invasive carcinoma, DCIS tended to be enhanced slowly. After performing MR examination in addition to mammography and ultrasonography, a more accurate diagnosis of disease extent was possible in 6 of 10 patients. MRI was useful in providing more precise information on the disease extent of DCIS, and it is considered useful in planning the type of surgery. Further study using larger series and precise pathological correlations are necessary.

Adult↗
PubMed2000

Ex vivo gene delivery using an adenovirus vector in treatment for cartilage defects.

OBJECTIVE: To realize local selective gene expression in grafted chondrocytes for cartilage defect, we investigated the usefulness of an ex vivo gene delivery method using an adenovirus vector. METHODS: Beta-galactosidase gene (LacZ) was transfected using an adenovirus vector to chondrocytes isolated from rat joints. The cells were then embedded into collagen gel, and LacZ expression in the gel was examined using 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining; beta-galactosidase activity was also measured. The collagen gel containing transfected chondrocytes was grafted to the experimental cartilage defects, and the expression of delivered gene was histologically examined after X-gal staining of the tissue containing the grafted area. RESULTS: X-gal positive chondrocytes in the gel accounted for 82% at one week and 55% at 8 weeks after gene delivery. Beta-galactosidase activity decreased with time, but its expression was maintained even at 8 weeks after gene delivery. Chondrocytes used in the allograft maintained their morphology, and the expression of delivered gene continued during the 8 week period. CONCLUSION: In this ex vivo method, delivered gene can be expressed efficiently for a long time; this method would be useful in allografts for cartilage defects.

Adenoviridae↗
PubMed2000

Hyaluronic acid inhibits the expression of u-PA, PAI-1, and u-PAR in human synovial fibroblasts of osteoarthritis and rheumatoid arthritis.

OBJECTIVE: Intraarticular administration of hyaluronic acid (HA) has been widely used for the treatment of osteoarthritis (OA). Fibrinolysis is closely related to the pericellular proteolysis involved in inflammation. However, the role of HA in the regulation of fibrinolytic factors is not yet known. We investigated the effect of HA on the pericellular fibrinolytic system of human synovial fibroblasts derived from OA and rheumatoid arthritis (RA). METHODS: Human synovial fibroblasts obtained from OA and RA were cultured in the presence and absence of HA. The antigen of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA, and u-PA activity was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunohistochemical analysis of u-PA were employed to detect u-PA receptor (u-PAR). RESULTS: HA suppressed the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium. Suppression of u-PA activity in OA synovial fibroblasts was more marked than in those of RA. The u-PA binding assay of OA and RA synovial fibroblasts revealed a single class of binding site: dissociation constant (Kd) 23.7 nM, maximal number of binding sites (Bmax) 3.11x10(4) binding sites/cell; Kd 16.5 nM, Bmax of 9.88x10(4) binding sites/cell, respectively. HA decreased Bmax in fibroblasts of both OA and RA. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease of the staining of u-PAR was more pronounced in the cells of RA than in OA. CONCLUSION: Pericellular fibrinolytic activity mediated by the u-PA/u-PAR system and PAI-1 was attenuated by HA in synovial fibroblasts derived from OA and RA. Thus, HA may be a useful agent to inhibit the inflammation of arthritis.

Adjuvants, Immunologic↗
PubMed2000

Value of the profundapopliteal collateral index for selecting between an in-flow and sequential arterial reconstruction in patients with multisegment arterial occlusive disease.

BACKGROUND: It remains difficult for surgeons to choose between an in-flow and sequential arterial reconstruction in patients with multisegment arterial occlusive disease. In addition, the exact criterion for the proper revascularization procedures of these patients also remains obscure. METHODS: The profundapopliteal collateral index (PPCI) was determined in all patients with occlusions of both the aortoiliac and superficial femoral arteries prior to undergoing an arterial bypass. The PPCI in the inflow bypass (IB) was also compared with the sequential bypass (SB). RESULTS: The symptoms of all patients undergoing either IB or SB improved. Preoperatively, the average PPCI in IB patients was significantly lower than that in SB patients. In addition, no significant difference was observed in the increased average rate of the ankle brachial index (ABI) between IB and SB. CONCLUSIONS: The PPCI is an accurate predictor of the hemodynamic potential of the geniculate collaterals. In cases with a low PPCI, especially in patients with multisegment arterial occlusive disease, in-flow procedures alone may often be sufficient for the successful treatment of such patients. The PPCI is thus considered to be useful for selecting the optimal revascularization procedures.

Aged↗